Human plasmacytoid dendritic cells are equipped with antigen-presenting and tumoricidal capacities

Abstract

Human plasmacytoid dendritic cells (pDCs) represent a highly specialized naturally occurring dendritic-cell subset and are the main producers of type I interferons (IFNs) in response to viral infections. We show that human pDCs activated by the preventive vaccine FSME specifically up-regulate CD56 on their surface, a marker that was thought to be specific for NK cells and associated with cytolytic effector functions. We observed that FSME-activated pDCs specifically lysed NK target cells and expressed cytotoxic molecules, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and granzyme B. Elevated levels of these molecules coincided with the expression of CD56, indicative for skewing human pDCs toward an interferon-producing killer DC subset. Detailed phenotypical and functional analysis revealed that pDCs attained a mature phenotype, secreted proinflammatory cytokines, and had the capacity to present antigens and stimulate T cells. Here, we report on the generation of CD56(+) human interferon producing killer pDCs with the capacity to present antigens. These findings aid in deciphering the role for pDCs in antitumor immunity and present a promising prospect of developing antitumor therapy using pDCs.

Antiviral Vaccines License T Cell Responses by Suppressing Granzyme B Levels in Human Plasmacytoid Dendritic Cells

“…Because T cell expansion, induced by various DC types, may contribute to a more profound cellular antiviral immune response after vaccination, the impact on DC appears to be of eminent importance for the effectiveness of an antiviral vaccine. Recent studies started to explore the effect of antiviral vaccines on the Agpresenting and tumoricidal capacity of DC including pDC (30,31,40). In our current study, we investigated how clinically used antiviral vaccines may impact on the GrB-mediated immunoregulatory potential of pDC.…”

“…Recently, pDC were shown to acquire an NK-like phenotype after stimulation with various vaccines, resulting in cytotoxic potential toward typical NK cell targets (31). Therefore, pDC may combine both regulatory effects on T cells and cytotoxic potential toward virus-infected or tumor cells.…”

“…Although the importance of pDC in antiviral immunity is widely accepted, their exact role during viral infections and vaccinations is not fully understood, and significant controversy exists regarding their immunogenic versus their tolerogenic potential (31,32). The general opinion is that pDC express and secrete large amounts of IFN-a after viral stimulation by which Ag-specific T cells and NK cells are activated (33).…”

“…Recently, it was reported that clinically used prophylactic vaccines modulate pDC-orchestrated immune responses (30,31). A detailed understanding of the mechanisms involved may be important for further improving such vaccines as both antiviral prophylaxis agents and as adjuvants in cancer immunotherapy.…”

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

“…Because pDCs produce high levels of type I IFNs in response to viral products, they play an important role in the detection and control of viral infections (4). Besides their antigen-presenting function, pDCs also display tumoricidal activity, although to a lesser extent than natural killer (NK) cells (5). mDCs specialize in mediating immunity against fungi and bacteria (2).…”